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Chapter 24

Pathogenic DNA Viruses

DNA Viruses

• DNA viruses that cause human disease are grouped into seven Families

• Classified based on the type of DNA they contain, the presence or absence of an envelope, size, and the host cells they attack

• Contain either double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) for their genome

• Double-stranded DNA viruses

• Poxviridae, Herpesviridae, Papillomaviridae, Polyomaviridae, and Adenoviridae

• Single-stranded DNA viruses

• Parvoviridae

• Viruses of the family Hepadnaviridae have a genome with both dsDNA and ssDNA

Poxviridae

• Double-stranded DNA viruses

• Have complex capsids and envelopes

• Largest viruses

• Infect many mammals

• Most animal poxviruses are species specific

• Unable to infect humans because they cannot attach to human cells

• Infection occurs primarily through the inhalation of viruses

• Close contact is necessary for infection by poxviruses

• Smallpox and molluscum contagiosum are the two main poxvirus diseases of humans

• Some diseases of animals can be transmitted to humans

• All poxviruses produce lesions that progress through a series of stages

Smallpox

• In the genus Orthopoxvirus

• Commonly known as variola

• Exists in two forms

• Variola major causes severe disease that can result in death

• Variola minor causes a less severe disease with a much lower mortality rate

• Both forms infect internal organs and then move to the skin where they produce pox

• Scars result on the skin, especially on the face

• Smallpox is the first human disease to be eradicated

• There are a number of factors that allowed eradication of smallpox

• Inexpensive, stable, and effective vaccine

• No animal reservoirs

• Obvious symptoms allow for quick diagnosis and quarantine

• Lack of asymptomatic cases

• Virus is only spread via close contact

Molluscum Contagiosum

• Caused by Molluscipoxvirus

• Spread by contact among infected children

• Sexually active adults can sometimes contract a genital form of the disease

• Skin disease characterized by smooth, waxy, tumorlike nodules on the face, truck, and limbs

• Virus produces a weak immune response

• Causes neighboring cells to divide rapidly thus acting like a tumor-causing virus

Other Poxvirus Infections

• Poxvirus infections also occur in animals

• Transmission of these poxviruses to humans require close contact with infected animals

• Infections of humans are usually mild

• Can result in pox and scars but little other damage

• Cowpox was used by Edward Jenner to immunize individuals against smallpox

Herpesviridae

• Viruses have enveloped polyhedral capsids and linear dsDNA

• Viruses attach to a host cell’s receptor and enter the cell through the fusion of its envelope with the cell membrane

• Herpesviruses are the most prevalent DNA viruses

• Herpesviruses are often latent

• They may remain inactive inside infected cells

• Viruses may reactivate causing a recurrence of manifestations of the disease

• Herpesviruses include various genera

• Simplexvirus, Varicellovirus, Lymphocryptovirus, Cytomegalovirus, Roseolovirus

• Herpesviruses are also designated by “HHV” (for “human herpesvirus”) and a number indicating the order in which they were discovered

Herpes Simplex Infections

• Often result in slowly spreading skin lesions

• Viruses of this genus are commonly known as herpes simplex virus or HSV

• 2 species of herpes simplex

• Herpes simplex virus type 1 (HSV-1)

• Herpes simplex virus type 2 (HSV-2)

Epidemiology and Pathogenesis of HSV Infections

• Active lesions are the usual source of infection

• Aysmptomatic carriers can shed HSV-2 genitally

• Transmission of the viruses occurs through close bodily contact

• Viruses enter the body through cracks or cuts in mucous membranes

• Skin lesions result from inflammation and cell death at the site of infection

• Herpes virions can spread from cell to cell through the formation of syncytia

• HSV-1 infections typically occur via casual contact in children

• HSV-2 infections are acquired between the ages of 15 and 29 from sexual activity

• Herpes infections often result in the recurrence of lesions

• Up to two-thirds of patients experience recurrences due to activation of the latent virus

Comparative Epidemiology and Pathology of Herpes Simplex Type 1 and Type 2 Infections

Diagnosis, Treatment, and Prevention

• Diagnosis

• Characteristic lesions, especially in the genital region and on the lips, is often diagnostic

• Virus can be easily cultured and typed.

• New serological tests are useful, when no lesions are present to culture

• Treatment

• HSV infections are among the few viral diseases that can be controlled with chemotherapeutic agents

• Topical applications of the drugs limit the duration of the lesions and reduce viral shedding

• The drugs don’t cure the diseases or free nerve cells of latent viral infections

• Prevention

• Health care workers should wear gloves to reduce exposure

• Sexual abstinence and sex between uninfected partners is the only prevention of HSV-2

Varicella-Zoster Virus Infections

• Commonly referred to as VZV

• Causes two diseases

• Varicella

• Often called chicken pox

• Typically occurs in children

• Herpes zoster

• Also called shingles

• Usually occurs in adults

Epidemiology and Pathogenesis of VZV Infections

• Chickenpox is a highly infectious disease seen most often in children

• Viruses enter the skin through the respiratory tract and the eyes

• Virus replicate at the site of infection then travel via the blood throughout the body

• Characteristic skin lesions appear 2-3 weeks after infection

• The disease is usually mild

• Chickenpox in adults is typically more severe than the childhood illness

• Latent virus can reactivate producing a rash known as shingles

• The rash is characteristic for its localization along a dermatome

Diagnosis, Treatment, and Prevention

• Diagnosis :Chickenpox is diagnosed from the characteristic lesions

• Shingles lesions can be more difficult to diagnose but localization along a dermatome is characteristic

• Treatment

• Chickenpox is usually self-limiting; symptoms are extreme pain and discomfort

• Shingles treatment involves management of the symptoms and bed rest;

• Prompt administration of antivirals can reduce or eliminate the pain.

• Prevention

• Difficult to prevent exposure to VZV because the viruses are shed from patients before obvious signs appear

Epstein-Barr Virus Infections

• Also referred to as EBV or HHV-4

• Can cause a number of different diseases

Epidemiology and Pathogenesis of EBV Infections

• Transmission of EBV usually occurs via saliva

• Virions initially infect the epithelial cells of the pharynx and parotid salivary glands

• The virus then enters the bloodstream where it invades the B lymphocytes

• The viruses become latent in B cells and immortalize them by suppressing apoptosis

• Symptoms of infectious mononucleosis arise from the immune response

• Cytotoxic T cells kill virus infected B lymphocytes

Diagnosis, Treatment, and Prevention

• Diagnosis

• Some diseases are easily diagnosed by their characteristic signs

• Other EBV infections have symptoms common to many pathogens

• Treatment

• Burkitt's lymphoma responds well to chemotherapy

• Mono patients are treated to relieve the symptoms

• Other EBV-induced conditions have no effective treatment

• Prevention

• Almost impossible because the viruses are widespread and transmitted readily by saliva

Cytomegalovirus

• Also referred to as CMV

• Cells infected with this virus become enlarged

• CMV infections is one of the more common infections of humans

• Transmission occurs through bodily secretions

• Requires close contact and a large exchange of secretion

• Usually occurs via sexual intercourse

• Also transmitted by in utero exposure, vaginal birth, blood transfusions, and organ transplants

• Most CMV infections are asymptomatic

• Fetuses, newborns, and immunodeficient patients can develop complications

• CMV can cause birth defects and may result in death

• AIDS patients or other immunocompromised adults may develop pneumonia, blindness, or cytomegalovirus mononucleosis, which is similar to infectious mononucleosis

Diagnosis, Treatment, and Prevention

• Diagnosis

• Dependent on the detection of the abnormally enlarged cells and inclusions within the nuclei of infected cells

• Treatment

• Treatment of fetuses and newborns is difficult because damage is usually done before the infection is discovered

• None of the drugs effective against other herpesviruses are effective against CMV

• Prevention

• Abstinence and safe sex can reduce the chance of infection

Other Herpesvirus Infections

• Human herpesvirus 6 (HHV-6)

• In the genus Roseolovirus

• Causes roseola which is characterized by a pink rash on the face, neck, trunk, and thighs

• Linked to multiple sclerosis by some researchers

• Can cause mononucleosis-like symptoms

• Infection with HHV-6 may make individuals more susceptible to AIDS

• Human herpesvirus 8 (HHV-8)

• Associated with Kaposi’s sarcoma, a cancer seen in AIDS patients

• The virus is not found in cancer-free patients or in normal tissues of victims

Papillomavirus Infections

• Causes papillomas, commonly known as warts

• Benign growths of the epithelium of the skin or mucous membranes

• Papillomas form on many body surfaces

• Often painful and unsightly

• Genital warts are associated with an increased risk of cancer

Epidemiology and Pathogenesis of Papillomavirus Infections

• Transmitted via direct contact and via fomites

• Can also be spread from one location to another on a given person by autoinoculation

• Viruses that cause genital warts invade the skin and mucous membranes during sexual intercourse

Diagnosis, Treatment, and Prevention

• Diagnosis

• Usually based on observation of the papillomas

• Diagnosis of cancers results from inspection of the genitalia and by a PAP smear in women

• Treatment

• Some warts can be removed through various methods

• Treatment of cancers involves radiation and chemical therapy

• Prevention

• Prevention of most types of warts is difficult

• Genital warts can be prevented by abstinence and perhaps safe sex

Polyomavirus Infections

• Capable of causing tumors in animals and humans

• Can cause other diseases

• BK and JC viruses are endemic worldwide

• The result of infections with these viruses depends on the individual’s immune system

• Normal immune systems tend to prevent latent infections

• Compromised immune systems allow latent infections to become established in the kidneys

• Reactivation events are different between the BK and JC viruses

• BK virus

• Reactivation can cause potentially severe urinary tract infections

• JC virus

• Can cause a rare disease called progressive multifocal leukoencephalopathy

• Viruses infect and kill the white matter of the central nervous system

• Paralysis and death eventually result

Adenoviridae

• Contain a single, linear dsDNA genome contained in a naked polyhedral capsid with spikes

• One of the causative agents of the common cold

• Spread via respiratory droplets

• Respiratory infections

• Viruses are taken into cells lining the respiratory tract via endocytosis

• Symptoms include sneezing, sore throat, cough, headache, and malaise

• Infection of the intestinal tract can produce mild diarrhea

• Infection of the conjunctiva can result in pinkeye

Hepadnaviridae

• Enveloped DNA viruses with icosahedral capsids

• The genome is composed of both single and double stranded DNA

• Includes the hepatitis B virus (HBV)

• HBV replicates through an RNA intermediary, a phenomenon unique among DNA viruses

• HBV invades and replicates in liver cells

Hepatitis B Infections

• Causes inflammation of the liver known as hepatitis

• HBV is the only DNA virus that causes hepatitis

• Viral infection can cause severe liver damage

• Symptoms can include jaundice, enlargement of the liver, abdominal distress, and bleeding into the skin and internal organs

• Coinfection with hepatitis D virus can increase the risk of permanent liver damage

Epidemiology and Pathogenesis of HBV Infections

• Virions are shed into saliva, semen, and vaginal secretions

• Transmission occurs when infected body fluids, particularly blood, come into contact with breaks in the skin or mucous membranes

• Spread can occur through infected needles, sexual intercourse, and passage to babies during childbirth

• Many infected individuals are asymptomatic or produce mild symptoms

• HBV has been shown to be associated with liver cancer

Diagnosis, Treatment, and Prevention

• Diagnosis

• Uses labeled antibodies to detect the presence of viral surface antigens released from HBV-infected cells

• Treatment

• No universally effective treatment

• The best treatment is prevention

• Prevention

• Vaccination and safer sexual practices has helped reduce the number of cases of hepatitis B

Parvoviridae

• Only human pathogen with a ssDNA genome

• Smallest of the DNA viruses

• Causes a number of diseases in animals

• B19 is the primary parvovirus of humans

• Causes erythema infectiosum, also called fifth disease

• Infection results in a reddening of the skin

• Sunlight aggravates the condition

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